Max Ludwig Henning Delbruck (1906–1981)

By Victoria Hernandez
Published: 2017-09-20
Keywords:

Max Ludwig Henning Delbruck (1906–1981)

Max Ludwig Henning Delbrück applied his knowledge of theoretical
physics to biological systems such as bacterial viruses called
bacteriophages, or phages, and gene replication during the twentieth
century in Germany and the US. Delbrück demonstrated that bacteria
undergo random genetic mutations to resist phage infections. Those
findings linked bacterial genetics to the genetics of higher organisms.
In the mid-twentieth century, Delbrück helped start the Phage Group and
Phage Course in the US, which further organized phage research. Delbrück
also contributed to the DNA replication debate that culminated in the
1958 Meselson-Stahl experiment, which demonstrated how organisms
replicate their genetic information. For his work with phages, Delbrück
earned part of the 1969 Nobel Prize for Physiology or Medicine.
Delbrück's work helped shape and establish new fields in molecular
biology and genetics to investigate the laws of inheritance and
development.

Delbrück was born on 4 September 1906, as the last of seven
children of Lina and Hans Delbrück, in Berlin, Germany. Delbrück grew up
in Grunewald, a suburb of Berlin. In 1914, World War I began. During the
war, Delbrück's family struggled with food shortages and in 1917
Delbrück's oldest brother died in combat. After the war ended in 1918,
Delbrück began to study astronomy. Some nights, Delbrück woke up in the
middle of the night to observe the stars with his telescope. He also
read about the seventeenth-century astronomer Johannes Kepler, who
studied planetary motion in late sixteenth and early seventeenth century
Germany. Delbrück graduated from high school in 1924 and wrote his
graduation speech on Kepler, using 300-year-old books from a nearby
library as his resources.

After graduating, Delbrück studied astronomy
and physics in college. In 1924, he first studied astronomy at the
University of Tübingen, in Tübingen, Germany. The following semester,
Delbrück attended the University of Berlin, later renamed Humboldt
University of Berlin, in Berlin, Germany, because his father taught
there and could not afford to pay for Delbrück's tuition elsewhere.
After switching between several German universities, in 1926 Delbrück
settled at the University of Göttingen, in Göttingen, Germany. Delbrück
initially pursued his PhD in astronomy at Göttingen, but later switched
to quantum physics, the study of the behavior of atomic and subatomic
particles. In Delbrück's biography, written by Ernst Peter Fischer and
Carol Lipson, the authors state that Delbrück switched fields because
German scientists made significant advancements in quantum physics that
made the field attractive. Furthermore, the literature on the topic was
primarily in German, whereas literature about astronomy research was in
English, which Delbrück could not read. In 1930, Delbrück received his
PhD for his work on the quantum aspects of a lithium atom.

Around the
time he completed his PhD, Delbrück began holding postdoctoral positions
throughout Europe and continued to do so during the 1930s. During the
summer of 1929, before Delbrück received his PhD, he started a
fellowship at the University of Bristol, in Bristol, England. At Bristol,
Delbrück gave lectures on quantum physics in spite of being unable to
speak English. In 1931, Delbrück received a one-year fellowship from the
Rockefeller Foundation, headquartered in New York City, New York, which
routinely funded scientists to perform research internationally. As part
of his fellowship, Delbrück worked with two Nobel laureates: Wolfgang
Pauli at the University of Zürich, in Zürich, Switzerland, and Niels Bohr
at the University of Copenhagen, in Copenhagen, Denmark.

Delbrück claimed
that his interest in biology stemmed from Bohr and their work together
in 1931. During a 1932 lecture titled "Light and Life" that Delbrück
attended, Bohr attempted to extend ideas of quantum physics to other
fields, including biology. Bohr spoke of a complementary phenomenon in
physics, in which matter exhibits particle and wave-like properties with
different laws governing each. He proposed that as with quantum physics,
complementary laws could be found in biology. Bohr stated that
scientists needed to find those complementary phenomena to fully explain
biology. According to Delbrück, the lecture inspired him enter the field
of biology.

After completing his Rockefeller fellowship in 1932, and
spending a few months at the University of Bristol, Delbrück returned to
Berlin to work at the Kaiser Wilhelm Institute of Chemistry, later
called the Max Planck Institute of Chemistry, where he remained from
1932 to 1937. In his position, Delbrück focused on quantum physics, but
he also pursued biology. For his biology pursuits, he launched
interdisciplinary research meetings that took place at his Berlin home in
Grunewald. Nikolai Timoféef-Ressovsky and Karl Günter Zimmer, who both
studied Drosophila, or fruit flies, in the 1900s, attended some meetings
and later collaborated with Delbrück to publish a paper in 1935 about
genetic mutation caused by radiation in Drosophila. That article was
Delbrück's first public contribution to biology. When Delbrück and his
colleagues published the paper, scientists still were not able to
explain the exact structure of genes, or whether genes were proteins or
nucleic acid. While some of the findings in the paper were not supported
by later research, quantum physicist Erwin Schrödinger obtained the
paper and talked about Delbrück's contributions to genetics in the book
What is Life? published almost ten years later. According to Delbrück's
biographers, many scientists, including DNA scientists James Watson and
Gunther Stent, wanted to work with Delbrück after reading What is Life?.
Delbrück's early contributions to genetics as mentioned by Schrödinger
made Delbrück known throughout the scientific community.

In the midst of
Delbrück's early work in biology, in 1937, the Nazi regime rose to power
in Germany. Subsequently, Delbrück left Germany for a Rockefeller
Foundation fellowship at the California Institute of Technology, or
Caltech, in Pasadena, California. The Nazi regime required all
university employees to participate in certain discussion groups. The
members of the Nazi party did not deem Delbrück politically mature
enough to hold a university position. In a later interview, Delbrück
claimed that he was most likely declined a position because he was too
vocal about his dislike of the Nazi party. Around the same time, the
Rockefeller foundation started a program to help the scientists Hitler
and the Nazi party had displaced. As part of that program, the
Rockefeller Foundation funded a position for Delbrück to work with the
Thomas Hunt Morgan research group to apply physics to studying the
genetics of mutations of Drosophila at Caltech. In June 1937, Delbrück
received his exit visa and left Germany.

Delbrück only briefly studied
Drosophila with the Morgan group before pursuing research on phages in
the US. In late 1937, Delbrück met Emory Ellis, a cancer researcher who
also studied bacteriophages at the Kerckhoff Laboratories of Biology at
Caltech. Delbrück took a tour of Ellis's lab, where Delbrück saw
phage¬-infected Escherichia colibacteria. While scientists later
utilized E. coli quite frequently, few scientists knew much about the
bacteria. In his interview with Harding, Delbrück commented on the
holes, called plaques, present in petri dishes where bacteria grew. On a
plate of bacterial cells, plaques appeared when bacteria died due to
phage infections. The presence of more phages lead to more
plaque-causing infections, so Ellis used the plaques to measure phage
growth. In 1938, Delbrück joined Ellis to work with phages. The two
researchers found a quantitative way to measure phage replication and
published their findings in 1939. Delbrück and Ellis's researched
enabled other phage scientists to more accurately measure phage
replication and study phage infections. The researcher's collaboration
ended when Ellis returned to his cancer research in 1939.

In 1939,
Delbrück renewed his Rockefeller Foundation fellowship for a position as
a physics instructor at Vanderbilt University in Nashville, Tennessee.
According to Delbrück, the start of World War II dissuaded him from
returning to Germany. After receiving the new position, in 1940 Delbrück
met Mary Adaline Bruce in Pasadena and phage researcher Salvador Luria
at a conference for the American Association for the Advancement of
Sciences in Philadelphia, Pennsylvania. The following year, Delbrück
married Bruce and began his major collaboration with Luria on phage
research.

From 1941 to 1943, Delbrück and Luria studied phages together.
During the summers, they worked in person at the Cold Spring Harbor
Laboratory in Cold Spring Harbor, New York. Throughout the rest of the
year, they worked separately, with Luria conducting the experiments and
Delbrück analyzing the data. Delbrück and Luria's research centered on
bacterial resistance to phages. Bacteria resistant to a particular phage
can continue to grow and divide even in the presence of that phage. At
the time, scientists proposed that genetic mutation caused the
resistance, but they did not know what caused the mutation. Researchers
had two hypotheses for the cause. They hypothesized that either the
mutations were spontaneous, as in other more complex organisms, or that
exposure to the phage induced the mutations. Delbrück and Luria aimed to
determine how the mutations arose.

The researchers worked with a strain
of E. coli that they knew could be infected by phages. In several
different petri dishes, they exposed E. coli to phages. The E. coli
divided rapidly. As the bacteria continued to replicate, different
mutations arose that made the bacteria resistant to the viral
infections. Therefore, Delbrück and Luria knew that the surviving
bacteria had undergone some mutation and that the dead bacteria did not
mutate. Delbrück and Luria exposed each petri dish to the same amount of
phage. If the mutations had been caused by exposure to the phage, all
the petri dishes would have exhibited the same number of surviving,
mutated bacteria. If the mutations were random, each petri dish would
contain a different number of surviving bacteria.

When analyzing the E.
coli after phage exposure, Delbrück and Luria noted that the number of
surviving bacterial colonies, or clusters, varied between petri dishes.
Some petri dishes had no colonies, meaning that the phages had killed
all the bacteria and that no bacteria mutated. Other petri dishes had
many colonies, indicating that many bacteria mutated to become resistant
to phage infection. The number of colonies fluctuated for the same
sample, leading Delbrück and Luria to conclude that that the
resistance-causing mutations were spontaneous and random. Delbrück and
Luria's experiment, called the Fluctuation Test, provided evidence that
genes in bacteria underwent random mutations and therefore behaved like
genes in higher organisms. Scientists later utilized bacterial genetics
to study gene expression and genetic engineering.

After performing the
Fluctuation Test with Luria, Delbrück continued to spend most of his
summers at the Cold Spring Harbor Laboratory. Initially, Delbrück spent
those summers alone studying phages, but later he and Luria made Cold
Spring Harbor a central location for scientists studying phages. The
scientists who met in Cold Spring Harbor later became members of the
Phage Group. The group unified phage research by encouraging cooperation
and collaboration among phage researchers. For example, in 1944 Delbrück
negotiated with other phage scientists to standardize the field by
agreeing to only study the same seven phage strains. The following year,
Delbrück introduced annual courses at the Cold Spring Harbor Laboratory
on phage genetics. The courses along with unofficial discussions among
scientists studying phages evolved into formal phage research meetings
held in Nashville in 1947, and then from 1950 onward in Cold Spring
Harbor. Annual phage meetings continued throughout the rest of
Delbrück's life.

In December 1946, Delbrück returned to Caltech to serve
as chair of the biology division. According to his biographers Fischer
and Lipson, Delbrück's early phage work with Luria did not help him with
his primary goal to understand phage replication. Rather than continue
to study mutations in bacteria, Delbrück moved his focus back to gene
replication, particularly in phages.

During the 1950s, Delbrück became
involved in a debate over the mechanics of DNA replication. In 1953,
James Watson and Francis Crick published their double helix model of
DNA, in which the two strands of DNA wound around each other like a
rope. At the time, scientists had just begun to accept DNA as genetic
material. Along with the model, Watson and Crick suggested a
self-replication mechanism of DNA that explained the passing of genetic
information from generation to generation or inheritance. The model,
later called semi-conservative replication, involved the two helical
strands of DNA unwinding and splitting apart to serve as individual
templates for new DNA strands. While some scientists immediately
accepted the mechanism, Delbrück questioned the model.

Delbrück
contested how DNA strands separated in the semi-conservative replication
mechanism. He questioned whether or not the two DNA strands could unwind
as Watson and Crick suggested and whether or not scientists could
actually experimentally test for the mechanism. In 1954, Delbrück wrote
his own theory for DNA replication, later called dispersive replication,
in which the DNA strands broke apart into smaller pieces to separate and
self-replicate. Delbrück also suggested ways in which scientists could
experimentally determine the method of DNA replication. Following the
publication of Delbrück's paper, scientists debated about how DNA
replicated and how they could determine what replication theory occurred
in nature. Delbrück and Stent, who also studied DNA and phages, followed
up the 1954 paper with a 1956 presentation outlining the new theories
and possible experiments. The DNA replication debate lasted until 1957,
when Matthew Meselson and Franklin Stahl conducted the Meselson-Stahl
experiment, which provided concrete evidence that DNA replicated
semi-conservatively, as Watson and Crick had suggested.

Also during the
1950s, Delbrück made another shift in his career. Delbrück began
studying the fungus Phycomyces and its signal transduction, or how it
responded to external stimuli like light, electricity, and surrounding
objects. Delbrück observed that during Phycomyces development, the
fungus altered its growth direction and growth rate temporarily in
response to different external stimuli. At the time, scientists did not
know how the external stimuli were translated into a growth response.
Like phage research in the 1930s and 1940s, signal transduction research
in Phycomyces was also fairly new. According to his biographer, in 1969,
Delbrück co-authored a review article on Phycomyces to recruit more
researchers into the field. In the 1970s, Delbrück also held group
meetings and workshops for Phycomyces research. Despite the efforts of
Delbrück and other scientists, they did not uncover the exact mechanism
for how Phycomyces responds to stimuli.

Delbrück made many efforts to
further science in post-World War II Germany. In 1956, Delbrück
co-founded the Institute of Genetics at the University of Cologne in
Cologne, Germany, where he served as director and guest professor from
1961 to 1963 during a leave of absence from his job at Caltech. Upon
request, Delbrück also served as a consultant at the University of
Konstanz in Konstanz, Germany. Furthermore, after World War II and
throughout the rest of his life, Delbrück mailed personal copies of
scientific journal articles to institutions in Germany that would have
otherwise not had access to the information.

Many figures in science and
history of science wrote about Delbrück's life through memoirs and
biographies. In 1988 Fischer, one of Delbrück's former graduate
students, and Lipson compiled Delbrück's autobiographical work and old
interviews to write his biography, Thinking About Science: Max Delbrück
and the Origins of Molecular Biology. Throughout personal recounts of
Delbrück's career, many authors highlight Delbrück's influence on other
scientists and fields in general. In particular, authors cite the Phage
Group, which gained a significant following. Throughout the twenty-six
years of phage courses and twenty-one years of phage meetings, the phage
group and phage course attracted hundreds of students and researchers
from the field of phage genetics. Delbrück also received recognition for
his work during his life, receiving many awards and honors. Among those,
Delbrück shared the Nobel Prize for Physiology or Medicine with Luria
and Alfred Hershey for his work regarding the nature of replication and
genetics in phages.

In 1978, doctors diagnosed Delbrück with multiple
myeloma, a bone marrow cancer. Despite attempts to treat the cancer
using chemotherapy, the cancer eventually led to Delbrück's death on 9
March 1981.